Pipecolic acid, an iminoacid related to lysine metabolism has been recently isolated in the mouse brain. It occurs in appreciable amounts (18 plus or minus 4 pmoles/g), it is synthesized in vitro and is taken up by a high affinity mechanism into synaptosomes. These findings from our laboratory suggest that pipecolic acid might occupy a central position in the cerebral lysine metabolism and play a physiological role in the brain. Moreover, abnormally high levels of pipecolic acid in brain and blood are correlated to severe and irreversible neurological damage in humans. We intend to continue our effort in order to elucidate lysine and pipecolc acid metabolism in mouse brain by focussing upon the following points: 1. Biosynthesis of pipecolic acid in vivo. Particular emphasis will be placed on the study of synthetic mechanisms in brain. This part will include the study of stable intermediate(s) as well as of the enzymes and cofactors involved in the synthesis of pipecolic acid. 2. Regional distribution of pipecolic acid in the mouse brain. This part includes autoradiographic studies. 3. Evaluation of the impact of exogenous supply of pipecolic acid and lysine upon its endogenous cerebral levels. This part includes experiments using special dies and starvation. 4. Transport of pipecolic acid in the brain and blood-brain barrier. 5. Uptake of pipecolic acid in synaptosomal fractions of brain reions. Characterization of the system and specificity. 6. Release of pipecolic acid from synaptosomal fractions of brain region. Chromatographic techniques associated with quantitative mass spectrometry as well as isotopic techniques and autoradiography will be used.